Mercuric chloride (HgCl2) is a well-known renal toxic that causes acute renal failure. The effect of HgCl2 treatment and the protection by thyroxine were studied in rat renal papilla (P), outer medullary inner stripe (OMIS), outer medullary outer stripe (OMOS) and cortical phospholipids (PhLs). HgCl2 brought about an increase in the total phospholipid content in P and OMIS but a drop in OMOS and cortex. Only phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn) accounted for such changes. Thyroxine, injected on HgCl2-treated rats, partially reversed the effect of the toxic metal in P and OMIS while completely reversed the PtdCho drop in OMOS and cortex. However, the hormone failed to recover the sphingomyelin increase in P, the PtdEtn shortage in OMIS, OMOS and partially reversed the drop in the cortex. When thyroxine was injected whith-out toxic treatment, no effect was observed in the phospholipid content of any kidney zone. Results obtained by using 32P as a precursor to study the PhL de novo synthesis were consistent with those of the phospholipid content. Thus, a radioactivity increase – associated with PtdCho and PtdEtn – was observed in the kidney zones where said endogenous PhLs had risen. But in OMOS and cortex, where PtdCho and PtdEtn had dropped, they were also accompanied by a decrease in radioactivity. The thyroxine-induced recovery phase also paralleled the phospholipid content results with those of the de novo synthesis. We suggest that the decrease in the renal phospholipid de novo synthesis may constitute one biochemical explanation of the selective renal toxic effect exerted by HgCl2 and that the increase observed in the renal phospholipid metabolism – induced by the toxic treatment in OMIS and P – may represent a protective mechanism of these zones against toxic injury. Moreover, recovery promoted by thyroxine treatment in OMOS and cortex was accompanied by the reversion of the corresponding PtdCho decrease induced by HgCl2.